Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children <18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p<0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p<0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p<0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

Revealing Cutinases’ Capabilities as Enantioselective Catalysts

The specific activity and enantioselectivity of immobilized cutinases from Humicola insolens (HiC) and Aspergillus oryzae (AoC) were compared with those of Lipase B from Candida antarctica (CALB) for a series of 1-phenylethanol (1-PEA) structural analogues. The aim was to understand their catalytic behavior by rationally studying three structural elements of the substrates: the length of the alkyl chain, the position of methylation of the aromatic ring, and the aromatic character of the ring. All enzymes were immobilized on the macroporous support Lewatit VP OC 1600 at loadings of ∼10% w/w. Docking studies revealed structural features of the enzymes that led to activity differences. All three enzymes exhibit (<i>R</i>)-selectivity. AoC, due to its more open and accessible active site, possesses high activity that exceeds in most cases that of HiC and CALB. By increasing the substrate’s alkyl chain length from methyl to <i>n</i>-propyl, the activity for the (<i>R</i>)-enantiomer of all three enzymes decreased significantly (≥70%), while the enantioselectivity of both cutinases was larger than that of CALB for the bulkier substrate. Methylation of the ring in the <i>ortho</i>-position led to loss of activity (≥55%); however, AoC retained substantial activity. For all three enzymes, the planar character of the substrate phenyl ring is crucial for stabilizing the substrate in the active sites via π–π stacking. HiC displays high enantioselectivity with most substrates, despite its wide active site, due to a “bottleneck” produced over the catalytic serine from Leu66 and Ile169